Atoris, 40 mg 30 pcs.

Prevention of heart attacks and strokes, Cholesterol, Reduction of cholesterol, Atherosclerosis

Hypercholesterolemia:

– to reduce elevated total cholesterol, LDL-C in adults with homozygous familial hypercholesterolemia as an adjunct to other hypolipidemic therapies (such as LDL-apheresis), or if such therapies are not available.

– Prevention of cardiovascular diseases:

– prevention of cardiovascular events in adult patients at high risk of developing primary cardiovascular events, as an adjunct to correction of other risk factors;

– secondary prevention of cardiovascular complications in patients with CHD to reduce mortality, MI, stroke, repeat hospitalizations for angina and the need for revascularization.

Active ingredient

Composition

1 film-coated tablet contains:nucleus

Active substance:

Atorvastatin calcium 41.44 mg, equivalent to atorvastatin 40.00 mg

Auxiliaries:

Povidone-K25, sodium lauryl sulfate, calcium carbonate, microcrystalline cellulose, lactose monohydrate, croscarmellose sodium, crosspovidone, magnesium stearate

Shell film

Opadray White Y-1-7000*

* Opadray White Y-1-7000:

Hypromellose, titanium dioxide (E171), macrogol-400

.

How to take, the dosage

Orally. To be taken at any time of the day, regardless of the time of meal.

Before starting treatment with Atoris®, one should try to achieve control of hypercholesterolemia through diet, exercise, and weight loss in obese patients as well as therapy for the underlying disease.

The patient should be advised a standard hypocholesterolemic diet when prescribing the drug and should adhere to it during the entire period of therapy.

The dose of Atoris® varies from 10 mg to 80 mg once daily and is chosen taking into account plasma concentration of LDL-C, purpose of therapy and individual response to therapy.

Maximum daily dose of Atoris® is 80 mg.

At the beginning of treatment and/or during dose increase of Atoris® it is necessary to monitor plasma lipid concentration every 2-4 weeks and adjust the drug dose accordingly.

Primary hypercholesterolemia and combined (mixed) hyperlipidemia

For most patients, the recommended dose of Atoris® is 10 mg once daily and the therapeutic effect is seen within 2 weeks and usually reaches a maximum after 4 weeks. With prolonged treatment, the effect is maintained.

Homozygous familial hypercholesterolemia

In most cases 80 mg once a day (decrease of plasma HC-LDL concentration by 18-45 %).

Heterozygous familial hypercholesterolemia

The initial dose is 10 mg per day. The dose should be adjusted individually and the relevance of the dose assessed every 4 weeks with a possible increase to 40 mg per day. Then either the dose can be increased to the maximum – 80 mg per day, or it is possible to combine bile acid sequestrants with intake of atorvastatin at a dose of 40 mg per day.

Prevention of cardiovascular diseases

In primary prevention studies, the dose of atorvastatin was 10 mg per day. It may be necessary to increase the dose in order to achieve LDL-C values in accordance with current recommendations.

Application in children 10 to 18 years of age for heterozygous familial hypercholesterolemia

The recommended starting dose is 10 mg once daily. The dose may be increased up to 80 mg daily depending on clinical effect and tolerability.

The dose of Atoris® should be selected depending on the goal of hypolipidemic therapy. Dose adjustment should be carried out at intervals of 4 weeks or more.

Liver function disorder

In patients with impaired liver function, the dose of Atoris® should be decreased with regular monitoring of serum activity of “liver” transaminases: aspartate aminotransferase (ACT) and alanine aminotransferase (ALT).

Kidney function disorder

Renal dysfunction does not affect atorvastatin concentration or decrease of plasma LDL-C concentration, therefore, no dose adjustment is required.

Elderly patients

There are no differences in therapeutic efficacy and safety of Atoris® in elderly patients compared to the general population; no dose adjustment is required (see section “Pharmacological properties. Pharmacokinetics”).

Simultaneous use with other drugs

If simultaneous use with cyclosporine, telaprevir or the combination tipranavir/ritonavir is necessary, the dose of Atoris® should not exceed 10 mg/day (see section “Special Precautions”).

Caution should be exercised and the lowest effective dose of atorvastatin should be used concomitantly with HIV protease inhibitors, hepatitis C virus protease inhibitors (boceprevir, elbasvir/grazoprevir, simeprevir), clarithromycin and itraconazole.In patients concomitantly using HCV antiviral drugs (elbasvir/grazoprevir) with atorvastatin, the dose of atorvastatin should not exceed 20 mg per day.

Interaction

During treatment with HMG-CoA reductase inhibitors, concomitant use of cyclosporine, fibrates, lipid-lowering nicotinic acid (more than 1 g/day) or CYP3A4 isoenzyme inhibitors (e.g., erythromycin, clarithromycin, antifungals – azole derivatives) increases the risk of myopathy (see See section “Special Precautions”).

CYP3A4 isoenzyme inhibitors

Since atorvastatin is metabolized by CYP3A4 isoenzyme, concomitant use of atorvastatin with CYP3A4 isoenzyme inhibitors may lead to increased plasma concentration of atorvastatin. The degree of interaction and potentiation effect is determined by the variability of effects on CYP3A4 isoenzyme.

It was found that potent inhibitors of CYP3A4 isoenzyme lead to a significant increase in plasma concentration of atorvastatin. If possible, avoid concomitant use of potent CYP3A4 isoenzyme inhibitors (such as cyclosporine, telithromycin, clarithromycin, delavirdine, stiripentol, ketoconazole, voriconazole, itraconazole, Pozaconazole, some HCV antiviral drugs (e.g., elbasvir/grazoprevir) and HIV protease inhibitors, including ritonavir, lopinavir, atazanavir, indinavir, darunavir, etc.).). If concomitant use of these drugs is necessary, the possibility of starting therapy with the minimum dose should be considered, and the possibility of reducing the maximum dose of atorvastatin should be assessed.

Moderate CYP3A4 isoenzyme inhibitors (such as erythromycin, diltiazem, verapamil and fluconazole) may lead to increased plasma concentration of atorvastatin. Against the background of concomitant use of HMG-CoA reductase inhibitors (statins) and erythromycin an increased risk of myopathy was noted. Studies of interaction of amiodarone or verapamil and atorvastatin have not been conducted. It is known that both amiodarone and verapamil inhibit CYP3A4 isoenzyme activity, and concomitant use of these drugs with atorvastatin may lead to increased atorvastatin exposure. In this regard, it is recommended to reduce the maximum dose of atorvastatin and conduct appropriate monitoring of the patient when concomitant use with moderate inhibitors of CYP3A4 isoenzyme. Monitoring should be performed after initiation of therapy and against the background of CYP3A4 isoenzyme inhibitor dose changes.

Gemfibrozil/fibrates

In the background of using fibrates in monotherapy, adverse reactions involving the musculoskeletal system, including rhabdomyolysis, have occasionally been noted. The risk of such reactions increases with concomitant use of fibrates and atorvastatin. If concomitant use of these drugs cannot be avoided, the lowest effective dose of atorvastatin should be used, and patients should be monitored regularly.

Ezetimibe

The use of ezetimibe is associated with the development of adverse reactions in the musculoskeletal system, including the development of rhabdomyolysis. The risk of such reactions increases with concomitant use of ezetimibe and atorvastatin. Close monitoring is recommended for these patients.

Eritromycin/Clarithromycin

concomitant usage of atorvastatin and erythromycin (500 mg 4 times daily) or clarithromycin (500 mg 2 times daily), CYP3A4 inhibitors, increased concentration of atorvastatin in plasma (see sections “Pharmacological properties. Pharmacokinetics” and “Cautions”).

Protease inhibitors

Concomitant use of atorvastatin with protease inhibitors, known as CYP3A4 isoenzyme inhibitors, is accompanied by an increase in plasma concentration of atorvastatin.

Diltiazem

Simultaneous administration of atorvastatin at a dose of 40 mg with diltiazem at a dose of 240 mg leads to increased concentration of atorvastatin in plasma (see section “Pharmacological properties. Pharmacokinetics”).

Cimetidine

no clinically significant interaction of atorvastatin with cimetidine was found (see section “Pharmacological properties. Pharmacokinetics”).

Itraconazole

Simultaneous administration of atorvastatin in doses from 20 mg to 40 mg and itraconazole in dose 200 mg led to the increase of AUC value of atorvastatin (see the section “Pharmacological properties. Pharmacokinetics”).

Grapefruit Juice

Since grapefruit juice contains one or more components that inhibit CYP3A4 isoenzyme, its excessive consumption (more than 1.2 L per day) may cause increase in plasma concentration of atorvastatin (see section “Pharmacological properties. Pharmacokinetics”).

Transport protein inhibitors

Atorvastatin is a substrate of liver enzyme transporters, OATP1B1 and OATP1B3 transporters. Metabolites of atorvastatin are substrates of OATP1B1. Atorvastatin is also identified as a substrate of efflux transporters MLU1 and BCRP, which may limit intestinal absorption and biliary clearance of atorvastatin (see section “Pharmacological properties. Pharmacokinetics”).

Simultaneous administration of atorvastatin at a dose of 10 mg and cyclosporine at a dose of 5.2 mg/kg/day resulted in increased systemic exposure of atorvastatin (AUC increase by 8.7 times) (see section “Pharmacological properties. Pharmacokinetics”). Cyclosporine is an inhibitor of transport polypeptide of organic anions 1B1 (OATP1B1), 1B3 (OATP1BZ), MDL1 and BCRP-associated protein and CYP3A4 isoenzyme, therefore, it increases atorvastatin systemic exposure. The daily dose of atorvastatin should not exceed 10 mg (see section “Dosage and administration”).

Elbasvir and grazoprevir are inhibitors of OATP1B1, OATP1BZ, MLU1 andBCRP; therefore, they increase the systemic effects of atorvastatin. Atoris® should be used with caution and in the lowest dose necessary (see section “Dosage and administration”).

CYP3A4 isoenzyme inducers

Concomitant use of atorvastatin with CYP3A4 isoenzyme inducers (e.g., efavirenz, rifampicin or St. John’s Wort preparations) may lead to decreased blood plasma concentration of atorvastatin. Due to the dual mechanism of interaction with rifampicin (inducer of CYP3A4 isoenzyme and inhibitor of hepatocyte transport protein OATP1B1), simultaneous use of atorvastatin and rifampicin is recommended, since delayed administration of atorvastatin after rifampicin administration leads to a significant decrease in plasma concentration of atorvastatin (see section “Pharmacological properties. Pharmacokinetics”). However, the effect of rifampicin on atorvastatin concentration in hepatocytes is unknown, and in case concomitant use cannot be avoided, the effectiveness of such a combination should be carefully monitored during therapy.

Antacids

Simultaneous oral administration of suspension containing magnesium hydroxide and aluminum hydroxide decreased atorvastatin plasma concentration (change in AUC: 0.66), but the degree of decrease of plasma LDL-C concentration was not changed.

Phenazone

Atorvastatin does not affect the pharmacokinetics of phenazone, so no interaction with other drugs metabolized by the same cytochrome system isoenzymes is expected.

Colestipol

Concomitant use of colestipol decreased plasma concentration of atorvastatin (AUC change: 0.74), but the hypolipidemic effect of the combination of atorvastatin and colestipol was superior to that of each drug alone.

Digoxin

The equilibrium plasma concentrations of digoxin and atorvastatin at a dose of 10 mg did not change when digoxin and atorvastatin were repeatedly administered. However, when using digoxin in combination with atorvastatin at a dose of 80 mg/day, digoxin concentration was increased (AUC change: 0.74). Patients receiving digoxin concomitantly with atorvastatin require appropriate monitoring.

Azithromycin

The concomitant use of atorvastatin 10 mg once daily and azithromycin 500 mg once daily did not change plasma concentration of atorvastatin.

Peroral contraceptive drugs

When atorvastatin and oral contraceptives containing norethisterone and ethinylestradiol were used concomitantly, a significant increase in AUC of norethisterone (AUC change: 1.28) and ethinylestradiol (AUC change: 1.19) was observed. This effect should be considered when choosing an oral contraceptive for a woman taking atorvastatin.

Terfenadine

No clinically significant changes in terfenadine pharmacokinetics have been observed with concomitant use of atorvastatin and terfenadine.

Varfarin

In a clinical study in patients regularly treated with warfarin, concomitant use of atorvastatin at a dose of 80 mg daily resulted in a slight increase in prothrombin time of approximately 1.7 seconds during the first 4 days of therapy. The index returned to normal within 15 days of atorvastatin therapy. Despite the fact that only in rare cases significant interaction affecting anticoagulant function was noted, it is necessary to determine prothrombin time before atorvastatin therapy in patients receiving coumarin anticoagulants therapy, and regularly – during therapy to prevent significant changes in prothrombin time. As soon as stable values of prothrombin time are noted, it can be controlled in the same way as recommended for patients receiving coumarin anticoagulants. If the dose of atorvastatin is changed or therapy is discontinued, control of prothrombin time should be performed according to the same principles as described above. Atorvastatin therapy has not been associated with the development of bleeding or changes in prothrombin time in patients who were not treated with anticoagulants.

Colchicine

Although studies of concomitant use of colchicine and atorvastatin have not been conducted, there have been reports of myopathy when using this combination. Caution should be exercised when concomitant use of atorvastatin and colchicine.

Amlodipine

In a drug interaction study in healthy volunteers, concomitant use of atorvastatin at a dose of 80 mg and amlodipine 10 mg resulted in a clinically insignificant increase in plasma concentration of atorvastatin (AUC change: 1.18).

Fusidic acid

In post-marketing studies, cases of rhabdomyolysis have been reported in patients taking statins, including atorvastatin and fusidic acid, simultaneously. The mechanism of this interaction is unknown. In patients for whom the use of fusidic acid is considered necessary, statin therapy should be discontinued for the duration of fusidic acid use. Therapy with statins may be resumed 7 days after the last fusidic acid administration. In exceptional cases, where prolonged systemic therapy with fusidic acid is necessary, such as for the treatment of severe infections, the necessity of simultaneous use of atorvastatin and fusidic acid should be considered on a case-by-case basis and under strict medical supervision. The patient should immediately seek medical attention if symptoms of muscle weakness, sensitivity or pain occur.

Other related therapy

In clinical trials atorvastatin was used simultaneously with hypotensive agents and estrogens as part of hormone replacement therapy. No signs of clinically significant adverse interactions have been observed, the studies of interaction with specific drugs have not been conducted.

In addition, increased concentrations of atorvastatin have been observed when used concomitantly with HIV protease inhibitors (with combinations of lopinavir and ritonavir, saquinavir and ritonavir, darunavir and ritonavir, with fosamprenavir, with combinations of fosamprenavir and ritonavir and with nelfinavir), hepatitis C protease inhibitors (boceprevir, elbasvir/grazoprevir, simeprevir), clarithromycin and itraconazole. Caution should be exercised when using these drugs concomitantly, and the lowest effective dose of atorvastatin should be used.

Special Instructions

In patients with the presence of risk factors for rhabdomyolysis (impaired renal function, hypothyroidism, hereditary muscle disorders in a patient in the history or in the family history, already suffered toxic effects of HMG-CoA reductase inhibitors [statins] or fibrates on muscle tissue, history of liver disease and/or patients who consume significant amounts of alcohol, age older than 70 years, situations in which atorvastatin plasma concentrations are expected to increase [e.g., interaction with other medicinal products]).

Contraindicated in persons under 18 years of age (insufficient clinical data on the effectiveness and safety of the drug in this age group), except for heterozygous familial hypercholesterolemia (use contraindicated in children under 10 years).

Use in children from 10 to 18 years old in heterozygous familial hypercholesterolemia.

The recommended initial dose is 10 mg once daily. The dose can be increased up to 80 mg per day depending on the clinical effect and tolerability.

In a 3-year study, there were no clinically significant effects on growth and puberty as measured by general maturation and development, Tanner stage scores, and height and body weight measurements.

In an 8-week open-label study, children with Tanner Scale scores of 1 (N = 15) and ≥2 (N = 24) (ages 6-17) with heterozygous familial hypercholesterolemia and baseline LDL-C concentrations ≥4 mmol/L received atorvastatin therapy as 5 mg or 10 mg chewable tablets or film-coated tablets at 10 mg or 20 mg once daily, respectively. The only significant covariate in the pharmacokinetic model of the population receiving atorvastatin was body weight. The apparent clearance of atorvastatin in children did not differ from that in adult patients when measured allometrically by body weight. In the range of atorvastatin and o-hydroxyatorvastatin there was a consistent decrease in LDL-C and CHD.

– Liver function disorder

In patients with impaired liver function, the dose of Atoris® should be decreased with regular monitoring of serum activity of “liver” transaminases: aspartate aminotransferase (ACT) and alanine aminotransferase (ALT).

Kidney function disorder

Renal dysfunction does not affect atorvastatin concentration or decrease of plasma LDL-C concentration, therefore, no dose adjustment is required.

Elderly patients

There are no differences in therapeutic efficacy and safety of Atoris® in elderly patients compared to the general population; no dose adjustment is required.

Impacts on the liver

As with other hypolipidemic agents of this class, treatment with atorvastatinone showed a moderate increase (more than 3 times the upper limit of normal) in the activity of “hepatic” transaminases ACT and ALT in blood plasma. A persistent increase in serum activity of “hepatic” transaminases (more than 3 times the upper limit of normal) was observed in 0.7% of patients receiving atorvastatin. Frequency of similar changes while using Atorvastatin in doses of 10 mg, 20 mg, 40 mg and 80 mg was 0.2%, 0.2%, 0.6% and 2.3%, respectively. Elevation of “hepatic” transaminases activity in blood plasma was usually not accompanied by jaundice or other clinical manifestations. When the dose of atorvastatin was decreased, temporarily or completely discontinued, plasma hepatic transaminase activity returned to the baseline level. Most patients continued taking atorvastatin in a reduced dose without any clinical consequences.

Hepatic function parameters should be monitored before therapy, 6 weeks and 12 weeks after the start of Atoris® or after increasing its dose. Liver function should also be monitored when clinical signs of liver damage appear. In case of increased plasma activity of “hepatic” transaminases, plasma ALT and ACT activity should be monitored until they normalize. If the increase of ACT or ALT activity in plasma more than 3 times compared to the upper limit of normal is maintained, it is recommended to reduce the dose or cancel the drug Atoris® (see section “Side effects”).

The drug Atoris® should be used with caution in patients who consume significant amounts of alcohol and/or have a history of liver disease. Active liver disease or persistently elevated blood plasma hepatic transaminases of unclear genesis are contraindications to the use of Atoris® (see section “Contraindications”).

Effects on skeletal muscles

Myalgia has been reported in patients receiving atorvastatin (see section “Side effects”). The diagnosis of myopathy should be assumed in patients with diffuse myalgia, muscle soreness or weakness and/or a marked increase in serum CPK activity (more than 10 times the upper limit of normal). Atoris® should be discontinued in case of marked increase in serum CPK activity, in the presence of confirmed or suspected myopathy. The risk of myopathy increases with concomitant use of drugs that increase the plasma concentration of atorvastatin (see sections “Interaction with other medicinal products” and “Pharmacological properties. Pharmacokinetics”), such as potent inhibitors of CYP3A4 isoenzyme or carrier proteins (e.g., cyclosporine, telithromycin, clarithromycin, delavirdine, stiripentol, ketoconazole, voriconazole, itraconazole, posaconazole, and HIV protease inhibitors, including ritonavir, lopinavir, atazanavir, indinavir, darunavir, tipranavir/ritonavir, etc.), gemfibrozil or other fibrates, HCV antivirals (boceprevir, telaprevir, elbasvir/grazoprevir), erythromycin, nicotinic acid at lipid-lowering doses (over 1 g/day), ezetimibe, azole antifungals, colchicine. Many of these drugs inhibit CYP3A4 isoenzyme-mediated metabolism and/or drug transport. It is known that CYP3A4 isoenzyme is the main liver isoenzyme involved in the biotransformation of atorvastatin. When using Atoris® in combination with fibrates, erythromycin, immunosuppressants, azole antifungal agents or nicotinic acid in lipid-lowering doses (more than 1 g/day), a physician should carefully weigh the expected benefit of treatment against the possible risk. Patients should be regularly monitored for muscle pain or weakness, especially during the first months of therapy and during the period of increasing the dose of any of these drugs. If combined therapy is necessary, consideration should be given to using lower initial and maintenance doses of the above agents (see section “Dosage and administration”). Concomitant use of atorvastatin and fusidic acid is not recommended, therefore temporary withdrawal of atorvastatin is recommended during treatment with fusidic acid. In such situations, periodic monitoring of serum CPK activity may be recommended, although such monitoring does not prevent the development of severe myopathy (see section “Interaction with other medicinal products”).

Before treatment

Atorvastatin should be administered with caution in patients with factors predisposing to the development of rhabdomyolysis. Before initiating therapy with atorvastatin, plasma CPK activity should be monitored in the following cases:

– renal function disorder,

– hypothyroidism,

– patient has a history or family history of hereditary muscle disorders,

– already suffered toxic effects of HMG-CoA reductase inhibitors (statins) or fibrates on muscle tissue,

– history of liver disease and/or patients consuming significant amounts of alcohol,

– in patients aged over 70 years old the necessity of plasma CPK control should be assessed, considering that these patients already have factors predisposing to rhabdomyolysis development,

– situations in which atorvastatin concentration in blood plasma is expected to increase, such as interactions with other medicinal products (see section “Interaction with other medicinal products”).

In such situations, the risk/benefit ratio should be assessed and the patient should be medically monitored.

When serum CPK activity is significantly elevated (more than 5 times the upper limit of normal), atorvastatin therapy should not be started.

Rare cases of rhabdomyolysis with acute renal failure due to myoglobinuria have been described with Atoris®, as with other HMG-CoA reductase inhibitors. Prior renal dysfunction may be a risk factor for rhabdomyolysis. Such patients should be monitored more closely for the musculoskeletal system. If there are symptoms of myopathy or risk factors of renal failure against the background of rhabdomyolysis (for example, severe acute infection, arterial hypotension, extensive surgery, trauma, metabolic, endocrine and water electrolyte disorders, uncontrolled convulsions) Atoris® therapy should be temporarily stopped or completely stopped.

Very rare cases of immune-mediated necrotizing myopathy during therapy or upon discontinuation of statins have been reported. Immune-mediated necrotizing myopathy is clinically characterized by persistent proximal muscle weakness and elevated serum CPK activity that persists despite discontinuation of statin treatment.

Cautions! Patients should be warned to seek immediate medical attention if they experience unexplained pain or muscle weakness, especially if accompanied by malaise or fever.

Stroke prevention by actively reducing plasma cholesterol concentrations (SPARCL)

In a retrospective analysis of stroke subtypes, patients without CHD who had recently had a stroke or TIA at baseline receiving atorvastatin at a dose of 80 mg/day had a higher incidence of hemorrhagic stroke compared with patients receiving placebo. The increased risk was particularly marked in patients with a history of hemorrhagic stroke or lacunar infarction at baseline. In this group of patients, the benefit/risk ratio when taking atorvastatin at a dose of 80 mg/day has not been defined, therefore, the possible risk of hemorrhagic stroke in these patients should be carefully evaluated before starting therapy.

After a specific analysis of a clinical trial involving 4,731 patients without CHD who had had a stroke or TIA within the previous 6 months and were prescribed atorvastatin 80 mg/day, they found a higher rate of hemorrhagic strokes in the atorvastatin group compared with the placebo group (55 in the atorvastatin group versus 33 in the placebo group). Patients with hemorrhagic stroke at the time of inclusion in the study had a higher risk for recurrent hemorrhagic stroke (7 in the atorvastatin group versus 2 in the placebo group). However, patients who received atorvastatin 80 mg/day had fewer strokes of any type (265 versus 311) and fewer cardiovascular events (123 versus 204).

Diabetes

Some evidence supports that HMG-CoA reductase inhibitors (statins) as a class can lead to elevated blood glucose concentrations, and individual patients at high risk for diabetes may develop a state of hyperglycemia requiring correction as in diabetes. However, this risk does not exceed the benefit of therapy with HMG-CoA reductase inhibitors (statins) in terms of vascular risks, so this may not be a reason to discontinue therapy. Patients related to the risk group (fasting blood glucose concentration from 5.6 to 6.9 mmol/l, BMI > 30 kg/m2 body surface area, elevated plasma TG concentration, arterial hypertension) should be under medical control, including monitoring of biochemical blood parameters, according to national guidelines.

Interstitial lung disease

Anecdotal cases of interstitial lung disease have been reported with some HMG-CoA reductase inhibitors (statins), especially during long-term therapy. Dyspnea, non-productive cough and deterioration of general health (fatigue, weight loss and fever) may be observed. If interstitial lung disease is suspected in a patient, atorvastatin therapy should be stopped.

Endocrine function

In the use of HMG-CoA reductase inhibitors (statins), including atorvastatin, there have been cases of increased HbA1 and fasting blood glucose concentrations. Nevertheless, the risk of hyperglycemia is lower than the degree of reduction of risk of vascular complications against the background of taking HMG-CoA reductase inhibitors (statins).

Application in children

There were no clinically significant effects on growth and puberty in the 3-year study as measured by general maturation and development, Tanner Scale staging, and height and body weight measurements.

Special information on excipients

The drug Atoris® contains lactose; therefore, it is contraindicated in the following conditions: lactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome.

There are no data about the effect of the drug Atoris® on the ability to drive vehicles and engage in potentially dangerous activities that require high concentration and quick psychomotor reactions. However, taking into account the possibility of development of dizziness, caution should be exercised when performing the listed activities.

Synopsis

Round, slightly biconvex, film-coated tablets, white or almost white.

Breakage appearance: a white, rough mass with a filmic coating of white or almost white color.

Contraindications

– Hypersensitivity to any component of the drug.

– Active liver disease or elevated plasma “hepatic” transaminase activity of unclear origin more than 3 times the upper limit of normal.

– Pregnancy.

– Period of breastfeeding.

– Women of childbearing age who are not using adequate methods of contraception.

– Age less than 18 years (there is insufficient clinical data on the effectiveness and safety of the drug in this age group), except for heterozygous familial hypercholesterolemia (use is contraindicated in children under 10 years of age).

– Simultaneous use with fusidic acid.

– Therapy with antiviral medicines of viral hepatitis C (HCV) glucaprevir/pibrentasvir.

Lactase deficiency, lactose intolerance, glucose-galactose malabsorption syndrome, because Atoris® contains lactose.

Side effects

The drug Atoris® is usually well tolerated, adverse reactions are usually mild and transient.

World Health Organization (WHO) recommended side effect frequency classification:

very often ≥ 1/10

often from ≥1/100 to < 1/10

infrequently from ≥ 1/1000 to < 1/100

rarely from ≥ 1/10000 to < 1/1000

very rarely < 1/10000

frequency unknown cannot be estimated from available data.

Infectious and parasitic diseases:

often: nasopharyngitis.

Blood and lymphatic system disorders:

rarely: thrombocytopenia.

Immune system disorders:

often: allergic reactions;

very rare: anaphylaxis.

Metabolic and nutritional disorders:

often: hyperglycemia;

infrequent: hypoglycemia, weight gain, anorexia;

incidence unknown: diabetes mellitus (incidence depends on the presence or absence of risk factors [fasting blood glucose concentration ≥ 5.6 mmol/L, body mass index [BMI] > 30 kg/m2 body surface area, elevated plasma TG concentration, history of hypertension]).

Mental disorders:

infrequent: “nightmare” dreams, insomnia;

frequency unknown: depression.

Nervous system disorders:

often: headache;

infrequent: dizziness, paresthesia, hypoesthesia, taste disorder, amnesia;

rarely: peripheral neuropathy;

frequency unknown: memory loss or decline.

Visual organ disorders:

infrequent: the occurrence of “shadows” before the eyes;

rarely: visual impairment.

Hearing organ and labyrinth disorders:

infrequent: tinnitus;

very rare: hearing loss.

Disorders of the respiratory system, thoracic and mediastinal organs:

often: sore throat, nosebleed;

incidence unknown: single cases of interstitial lung disease (usually with long-term use).

digestive system disorders:

often: constipation, flatulence, dyspepsia, nausea, diarrhea;

infrequent: vomiting, abdominal pain, belching, pancreatitis, abdominal discomfort.

Liver and biliary tract disorders:

infrequently: hepatitis;

rarely: cholestasis.

Skin and subcutaneous tissue disorders:

infrequent: urticaria, skin itching, skin rash, alopecia;

seldom: angioneurotic edema, bullous rash, erythema multiforme (including Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell’s syndrome).

Musculoskeletal and connective tissue disorders:

often: myalgia, arthralgia, pain in extremities, muscle cramps, joint swelling, back pain, skeletal muscle pain;

infrequent: neck pain, muscle weakness;

rarely: myopathy, myositis, rhabdomyolysis, tendonitis (in some cases with tendon rupture), muscle tear;

very rarely: lupus-like syndrome;

frequency unknown: immune-mediated necrotizing myopathy.

Kidney and urinary tract disorders:

very rarely: secondary renal failure.

Gender and breast disorders:

infrequently: impotence;

very rare: gynecomastia.

General disorders and disorders at the point of administration:

infrequent: malaise, asthenic syndrome, chest pain, peripheral edema, increased fatigue, fever.

Laboratory and instrumental data:

often: abnormal results of “liver” tests (ACT and ALT) in plasma, increased serum creatine phosphokinase (CPK) activity;

infrequent: leukocyturia;

frequency unknown: increased glycosylated hemoglobin (HbAl) concentration.

Overdose

There is no specific antidote for treatment of overdose with Atoris®. In case of overdose, symptomatic treatment should be administered as necessary. Liver function tests should be performed and serum CPK activity should be monitored. Since atorvastatin is actively bound to blood plasma proteins, hemodialysis is ineffective.

Pregnancy use

The drug Atoris® is contraindicated in pregnancy.

Women of reproductive age should use adequate contraceptive methods during treatment. The use of Atoris® is contraindicated in women of childbearing age who do not use adequate contraception methods.

Rare cases of congenital abnormalities have been reported following fetal exposure to HMG-CoA reductase inhibitors (statins) in utero. Toxic effects on reproductive function have been shown in animal studies. Atoris® is contraindicated during lactation. It is unknown whether atorvastatin is excreted with breast milk. If it is necessary to prescribe the drug during lactation, breastfeeding should be stopped to avoid the risk of adverse effects in infants.

Similarities